Israel Medical Association Journal

Background: The parasympathetic system and its main neurotransmitter, acetylcholine, contributes to homeostasis of inflammation. Cholinergic dysregulation is thought to contribute to the pathogenesis of inflammatory rheumatic diseases. Cholinesterase activity in patients with psoriatic arthritis (PsA) has not been investigated.

Objectives: To compare the cholinesterase activity in patients with PsA and immunocompetent controls and to explore the correlation between cholinergic status (CS) and PsA disease activity.

Methods: Serum acetylcholinesterase (AChE) and total cholinesterase activity were measured in patients with PsA (n=88) and matched controls (n=84). Cholinergic activity before and 3–6 months after the initiation of a biologic treatment was evaluated in seven patients with PsA.

Results: The levels of AChE and CS were similar in both PsA patients and controls. PsA patients treated with biologics had significantly lower levels of AChE and CS compared to patients treated with non-biologics: 447.4 vs. 526 substrate hydrolyzed/min/ml, P = 0.005, and 1360.9 vs. 1536, P = 0.029, respectively. We found an association between C-reactive protein levels, AChE activity (r = 0.291, P = 0.008), and cholinergic status (r = 0.247, P = 0.026) in patients with PsA but not in controls. No correlation between AChE activity, cholinergic status, and the indices of PsA disease activity was found. After initiating or switching biologic treatment in 7 patients, AChE levels remained stable.

Conclusions: We demonstrated similar cholinesterase activity in patients with psoriatic arthritis and controls, highlighting a potential effect of biologic treatment on cholinergic activity in patients with PsA.

Fever of unknown origin (FUO) is defined as the repeated occurrence of elevated body temperature above 38.3°C (101°F) lasting for at least 3 weeks with no clear diagnosis despite a thorough investigation of more than one-week duration. FUO cases could be categorized into three major etiologies: infectious, neoplastic, and systemic inflammatory. Despite novel diagnostic modalities, clinicians still encounter a significant number of unresolved FUO cases, accounting for as many as 50% of cases [1]. Prolonged futile FUO investigations may be a source of frustration for many clinicians [2]. We described a unique cause for FUO that shares the complexity of the diagnostic workup and emphasizes the importance of ¹⁸F-fluorodeoxyglucose positron-emission tomography/computed tomography (PET/CT) modality in the process of investigating FUO.

Background: Acute kidney injury (AKI) is a risk factor for morbidity and mortality during critical illness especially in very old patients admitted to intensive care units.

Objectives: To identify prognostic markers for AKI patients.

Methods: This single-center retrospective study was based on a patient registry of a medical intensive care unit. Hospital records of patients aged 80 years or older admitted between 2005 and 2015 were examined. Patients who developed AKI according to Kidney Disease: Improving Global Outcomes (KDIGO) guidelines within 4 days of admission were included in this study.

Results: The study comprised 96 patients with AKI and 81 age- and sex-matched controls without AKI. Mean acute physiology and chronic health evaluation (APACHE) II score was 30 with an ICU mortality of 27% in very old patients with AKI. The odds ratio of hospital mortality for these patients was 5.02 compared to controls (49% vs. 16%). APACHE II score and fluid balance in the first 2 days of ICU admission were the strongest predictors of ICU mortality with an area under the receiver operating characteristic of 0.76. Of the 47 patients with AKI who survived hospital admission, 30 were discharged home.

Conclusions: Mortality was increased in very old ICU patients with AKI. Among survivors, two-thirds returned home.

Background: Granulomatosis with polyangiitis (GPA) otologic manifestations include conductive and sensorineural hearing loss (HL). Vasculitis is assumed to be the primary cause of otologic manifestations. Deaf patients and patients with HL who do not benefit from hearing aids can benefit from cochlear implants (CI). There are currently no specific guidelines for treatment of patients with GPA suited for CI.

Objectives: To assess whether patients who are deaf due to GPA are good candidates for CI and if prior surgical or medical treatment of the inflammation are needed.

Methods: A case report is presented.

Results: A 71-year-old female patient with GPA and bilateral profound HL underwent CI. Prior to CI, preparation consisted of audiological evaluations by an otolaryngologist and a rheumatologist, followed by a course of prednisone and methotrexate for middle ear and nasal inflammations. CI was performed with no complications. The speech reception threshold and the monosyllabic word discrimination score after surgery were 25 dBHL and 75%, respectively.

Conclusions: Inflammation due to GPA can be controlled medically with immunosuppressive medications without subtotal petrosectomy, as in chronic suppurative otitis media. Satisfactory audiological results can be expected.

Background: Secondary immune thrombocytopenic purpura (ITP) associated with coronavirus disease 2019 (COVID-19) is a rare but serious complication of the pandemic. Diagnostic criteria include clinical and laboratory findings. Early treatment is often effective, but rare severe bleeding and death can occur. An autoimmune mechanism is likely.

Objectives: To determine a role for molecular mimicry in producing disease.

Methods: Hexapeptide and heptapeptide matches between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and platelet N-glycosylated proteins and other human proteins were assessed.

Results: Shared viral and platelet glycoprotein peptides were found. Copy frequency of these peptides in the human proteome was low for many of the candidate molecular mimics.

Conclusions: The data support a contribution of molecular mimicry in COVID-19 ITP autoimmunity and offer avenues for in vitro diagnostic assay development. The continuation of the pandemic necessitates additional understanding of COVID-19 ITP as well as studies on diagnosis and mitigation.

Background: Multiple myeloma (MM) affects the long bones in 25% of patients. The advent of positron-emission tomography/computed tomography (PET/CT) scanners offers the possibility of both metabolic and radiographic information and may help determine fracture risk. To the best of our knowledge, no published study correlates these two factors with long bone fractures.

Objective: To evaluate the impact of PET/CT on fracture risk assessment in multiple myeloma patients.

Methods: We identified all bone marrow biopsy proven multiple myeloma patients from 1 January 2010 to 31 January 2015 at a single institution. We prospectively followed patients with long bone lesions using PET/CT scan images.

Results: We identified 119 patients (59 males/60 females) with 256 long bone lesions. Mean age at diagnosis was 58 years. The majority of lesions were in the femur (n=150, 59%) and humerus (n=84, 33%); 13 lesions in 10 patients (8%) required surgery for impending (n=4) or actual fracture (n=9). Higher median SUVmax was measured for those with cortical involvement (8.05, range 0–50.8) vs. no involvement (5.0, range 2.1–18.1). SUVmax was found to be a predictor of cortical involvement (odds ratio = 1.17, P = 0.026). No significant correlation was found between SUVmax and pain or fracture (P = 0.43).

Conclusions: Improved medical treatment resulted improvement in 8% of patients with an actual or impending fracture. The orthopedic surgeons commonly use the Mirels classification for long bone fracture prediction. Adding PET/CT imaging to study in myeloma long bone lesions did not predict fracture risk directly but suggested it indirectly by cortical erosion.

Background: In Israel, critically ill patients are ventilated and managed in intensive care units or general wards.

Objectives: To compare the mortality rates and long-term cognitive and functional outcomes of ventilated patients who underwent tracheostomy insertion in the Medical ICU (MICU) versus those cared for in the in-patient wards.

Methods: The study comprised 170 patients who underwent percutaneous dilatational tracheostomy (PDT) over an 18-month period in the MICU (n=102) and in in-patient wards (internal medicine and neurology) (n=68). Telephone interviews were conducted with living patients and/or their relatives at least 6 months after discharge from the hospital.

Results: Ward patients were 10 years older than ICU patients undergoing PDT (P = 0.003). The length of stay (LOS) in the wards was longer than in the ICU (P < 0.001), whereas the total LOS in the hospital was similar (P = 0.43). ICU mortality was lower than in the wards (P = 0.001) but hospital mortality was comparable between the two groups (P = 0.17). At 6 months follow-up more ICU patients were fully conscious, weaned from ventilation, and decannulated. More patients in the ICU group were at home and were independent or had mildly impaired activities of daily living. More patients in the ward group were residing in long-term care facilities with functional limitations.

Conclusions: MICU patients who undergo tracheostomy may have a good long-term functional and cognitive outcome. More studies are needed to further assess long-term outcomes in these patients.

The authors reviewed the two most common current uses of brain ¹⁸F-labeled fluoro-2-deoxyglucose positron emission tomography (FDG-PET) at a large academic medical center. For epilepsy patients considering surgical management, FDG-PET can help localize epileptogenic lesions, discriminate between multiple or discordant EEG or MRI findings, and predict prognosis for post-surgical seizure control. In elderly patients with cognitive impairment, FDG-PET often demonstrates lobar-specific patterns of hypometabolism that suggest particular underlying neurodegenerative pathologies, such as Alzheimer’s disease. FDG-PET of the brain can be a key diagnostic modality and contribute to improved patient care.

Falling from a height accounts for 14.1% of all hospital admissions for traumatic injury. In 5% of cases, the injury is severe or critical, and in 1.5%, it is fatal. The dangers of falling have been recognized since time immemorial. Indeed, the Bible instructs us to build a parapet around the roof of our home so that, “…you may not bring the guilt of bloodshed on your house if someone falls from it” (Deuteronomy 22:8). This commandment highlights the relatively simple and practical means by which we can prevent falls. It is also one of a series of ethical laws that are presented to help us understand and obey the larger Biblical precepts of loving one’s neighbor and guarding the sanctity of life. The concept teaches us that it is the responsibility of all individuals to be cognizant of others and to avoid harming people through negligence or carelessness. The aim of this article is to explain the commandment to build a parapet in the context of the risk of falling from a height and to expand on its wider implications. The present work was prompted in part by the alarming increase in fatal and near-fatal accidents in Israel in two particular populations.

Background: Whole-body integrated positron emission tomography / contrast-enhanced computed tomography (PET/CT) scan is increasingly used in cutaneous lymphomas. However, the value of PET/CT in the detection of cutaneous lesions in primary cutaneous B-cell lymphoma (PCBCL) has barely been investigated.

Objectives: To investigate the diagnostic accuracy of PET/CT in tracking cutaneous involvement in PCBCL.

Methods: A retrospective study was conducted on 35 consecutive patients diagnosed with cutaneous B-cell lymphoma according to the World Health Organization classification who were evaluated with PET/CT as the initial staging procedure before treatment.

Results: Thirty-five patients met the study criteria. In two patients extracutaneous disease was detected by PET/CT and CT and confirmed by biopsy. Of the 33 patients with PCBCL, 26 (79%) had small cell PCBCL (18 marginal-zone, 8 follicle-center lymphoma) and 7 (21%) had large cell PCBCL (3 follicle-center, 3 leg-type, 1 indeterminate). PET/CT detected skin lesions in 3 of 26 patients (12%) with small-cell PCBCL as compared to 6 of 7 patients with large-cell PCBLC (86%), a 7.4-fold detection risk (95% confidence interval, 2.4–22, P = 0.004). The PET-positive subgroup was characterized by larger lesion size (P < 0.001) and a higher Ki-67 proliferation index (P < 0.001).

Conclusions: The sensitivity of PET/CT for detecting cutaneous involvement of lymphomas is low for small-cell PCBCL but high for large-cell types, and thus may facilitate therapeutic strategies.